Noninvasive localized MR quantification of creatine kinase metabolites in normal and infarcted canine myocardium.

PURPOSE To develop image-guided spatially localized magnetic resonance (MR) spectroscopy to provide a noninvasive quantitative probe of myocardial creatine kinase (CK) metabolism, and to use it to determine the extent of changes in CK energy metabolism in nonviable infarcted canine myocardium. MATERIALS AND METHODS Water-referenced localized phosphorus and proton MR spectroscopy were combined in a single protocol to noninvasively measure phosphocreatine (PCr), adenosine triphosphate (ATP), and total of phosphorylated and unphosphorylated creatine (CR) concentrations and pH in the myocardium in six normal dogs and six dogs with surgically induced myocardial infarction. Unphosphorylated creatine and adenosine diphosphate (ADP) levels were calculated. The results were compared with biochemical measurements at postmortem biopsy. RESULTS Significant reductions in PCr-to-ATP ratios (1.7 +/- 0.3 [SD] vs 1 +/- 0.4; P <.001), PCr (10.3 +/- 2.1 vs 4.3 +/- 2.0 micromol/g wet weight; P <.0001), ATP (6.4 +/- 1.4 vs 3.7 +/- 1.4 micromol/g wet weight; P <.001), and CR (24.7 +/- 6.1 vs 6.3 +/- 3.7; P <.0001) were measured noninvasively in infarcted, as compared with normal, tissue. Biopsy measurements confirmed infarct-related reductions observed at MR spectroscopy, although high-energy phosphate concentrations were lower at biopsy. ADP calculated from noninvasive MR spectroscopic measurements was 0.11 +/- 0.07 micromol/g wet weight in normal myocardium. CONCLUSION This combined phosphorus and proton MR spectroscopic approach provides a near-complete picture of in vivo myocardial CK metabolism in normal and diseased heart and a tool for noninvasively measuring metabolite reductions associated with the loss of viability.

[1]  P A Bottomley,et al.  Total creatine in muscle: imaging and quantification with proton MR spectroscopy. , 1997, Radiology.

[2]  J. Ingwall.  Is cardiac failure a consequence of decreased energy reserve , 1993 .

[3]  K Uğurbil,et al.  31P NMR spectroscopy of the human heart at 4 T: Detection of substantially uncontaminated cardiac spectra and differentiation of subepicardium and subendocardium , 1992, Magnetic resonance in medicine.

[4]  P A Bottomley,et al.  The fate of inorganic phosphate and pH in regional myocardial ischemia and infarction: A noninvasive 31P NMR study , 1987, Magnetic resonance in medicine.

[5]  C J Hardy,et al.  Phosphate metabolite imaging and concentration measurements in human heart by nuclear magnetic resonance , 1990, Magnetic resonance in medicine.

[6]  S. Neubauer,et al.  31P Magnetic Resonance Spectroscopy in Dilated Cardiomyopathy and Coronary Artery Disease: Altered Cardiac High‐Energy Phosphate Metabolism in Heart Failure , 1992, Circulation.

[7]  T. Inubushi,et al.  Quantitative measurements of cardiac phosphorus metabolites in coronary artery disease by 31P magnetic resonance spectroscopy. , 1995, Circulation.

[8]  G. Pohost.  Is 31P-NMR spectroscopic imaging a viable approach to assess myocardial viability? , 1995, Circulation.

[9]  E. E. van der Wall,et al.  Cardiac metabolism in patients with dilated and hypertrophic cardio‐myopathy: Assessment with proton‐decoupled P‐31 MR spectroscopy , 1992, Journal of Magnetic Resonance Imaging.

[10]  P. Bottomley,et al.  Non-invasive magnetic-resonance detection of creatine depletion in non-viable infarcted myocardium , 1998, The Lancet.

[11]  Jullie W Pan,et al.  3D 31P Spectroscopic Imaging of the Human Heart at 4.1 T , 1995, Magnetic resonance in medicine.

[12]  C J Hardy,et al.  Rapid 31P spectroscopy on a 4‐T whole‐body system , 1988, Magnetic resonance in medicine.

[13]  J. Ingwall,et al.  Impaired cardiac energetics in mice lacking muscle-specific isoenzymes of creatine kinase. , 1998, Circulation research.

[14]  S. Souza,et al.  A broadband phased‐array system for direct phosphorus and sodium metabolic MRI on a clinical scanner , 2000, Magnetic resonance in medicine.

[15]  B Jung,et al.  Methods and reproducibility of cardiac/respiratory double‐triggered 1H‐MR spectroscopy of the human heart , 1999, Magnetic resonance in medicine.

[16]  R. Shemin,et al.  The creatine kinase system in normal and diseased human myocardium. , 1985, The New England journal of medicine.

[17]  T. Inubushi,et al.  In vivo 31P nuclear magnetic resonance spectroscopy in patients with old myocardial infarction. , 1992, Japanese circulation journal.

[18]  A. Wechsler,et al.  Derangements in myocardial purine and pyrimidine nucleotide metabolism in patients with coronary artery disease and left ventricular hypertrophy. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[19]  R. Herfkens,et al.  Altered phosphate metabolism in myocardial infarction: P-31 MR spectroscopy. , 1987, Radiology.

[20]  M. Weisfeldt,et al.  Mechanisms of Ischemic Myocardial Cell Damage Assessed by Phosphorus‐31 Nuclear Magnetic Resonance , 1982, Circulation.

[21]  A. Haase,et al.  Three‐dimensional 31P magnetic resonance spectroscopic imaging of regional high‐energy phosphate metabolism in injured rat heart , 1998, Magnetic resonance in medicine.

[22]  P A Bottomley,et al.  MR spectroscopy of the human heart: the status and the challenges. , 1994, Radiology.

[23]  C. Lenfant.  Report of the Task Force on Research in Heart Failure. , 1994, Circulation.

[24]  D Hahn,et al.  Concentrations of human cardiac phosphorus metabolites determined by SLOOP 31P NMR spectroscopy , 1999, Magnetic resonance in medicine.

[25]  M. D. De Buyzere,et al.  Creatine Determinations as an Early Marker for the Diagnosis of Acute Myocardial Infarction , 1988, Annals of clinical biochemistry.

[26]  S. Vatner,et al.  Progressive loss of myocardial ATP due to a loss of total purines during the development of heart failure in dogs: a compensatory role for the parallel loss of creatine. , 1999, Circulation.

[27]  D. S. Williams,et al.  31P NMR measurements of myocardial pH in vivo. , 1988, Biochemical and biophysical research communications.

[28]  R. Jennings,et al.  Lethal myocardial ischemic injury. , 1981, The American journal of pathology.

[29]  S. Morikawa,et al.  Detection of myocardial ischemia by 31P magnetic resonance spectroscopy during handgrip exercise. , 1994, Circulation.

[30]  P A Bottomley,et al.  Human cardiac high‐energy phosphate metabolite concentrations by 1D‐resolved NMR spectroscopy , 1996, Magnetic resonance in medicine.

[31]  P A Bottomley,et al.  Optimum flip‐angles for exciting NMR with uncertain T1 values , 1994, Magnetic resonance in medicine.

[32]  C. Hardy,et al.  Proton overhauser enhancements in human cardiac phosphorus NMR spectroscopy at 1.5 T , 1992, Magnetic resonance in medicine.

[33]  C. Gibbs.  The cytoplasmic phosphorylation potential. Its possible role in the control of myocardial respiration and cardiac contractility. , 1985, Journal of molecular and cellular cardiology.